The site and mode of action whereby perfusion with oxidized glutathione enhances fluid transport across the corneal endothelium in vitro is unknown and may involve effects on the plasma membrane and/or intracellular metabolic events. Methods to assess membranous effects will be based on the effect of thiol-blocked derivatives or thiol-blocking compounds on the physiological parameter of stromal thinning and/or such pertinent biochemical parameters as the intracellular level of reduced and oxidized glutathione. Further efforts toward synthesizing soluble polysaccharide derivatives of oxidized glutathione or cystine (molecularly sized to obstruct cellular permeation) will be made. If effective in supporting fluid transport, cellular interiorization by fluid-phase or adsorptive endocytosis will have to be assessed by concentration, temperature- and time-dependency of incorporation of a suitable tracer. A reduction in the protein thiol:disulfide ratio and the increase of insoluble protein that occurs during aging of the normal adult lens is markedly accelerated in senile cataract. Treatment of lens insoluble proteins with borohydride, in addition to reducing disulfides, was found to produce trichloroacetic acid soluble, thiol-containing fragments in greater amounts from the nuclear region of cataractous than normal lenses. Efforts are being made to separate these fragments by gel and ion exchange chromatography and to characterize them by terminal end group and amino acid sequence analyses.